The researchers say that the vessels are "very well hidden," explaining why it has taken so long for them to be identified.
Image credit: The University of Virginia
Jonathan Kipnis, a professor in The University of Virginia's (UVa) Department of Neuroscience and director of UVa's Center for Brain Immunology and Glia, says his team's discovery "changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions."
Not only is it surprising that the vessels connecting these two bodily systems have escaped detection for so long - when the lymphatic system has been so comprehensively studied - but the researchers say the discovery could have a huge impact on the study and treatment of neurological diseases such as autism, Alzheimer's disease and multiple sclerosis.
"Instead of asking, 'How do we study the immune response of the brain?', 'Why do multiple sclerosis patients have the immune attacks?', now we can approach this mechanistically," Prof. Kipnis explains, "because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels."
These secretive vessels were detected thanks to the work of a postdoctoral fellow in Prof. Kipnis' lab, Antoine Louveau, who developed a new method to count the membranes covering the brains of a mouse on a single slide. This involved securing the membranes - called meninges - to the skullcap before dissection.
Louveau then noticed a vessel-like pattern in the distribution of the immune cells he was examining.
"I called Jony [Kipnis] to the microscope and I said, 'I think we have something,'" Louveau recalls.
A simple test for lymphatic vessels confirmed their presence.
"I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped," Prof. Kipnis says. "I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not."
Prof. Kipnis says that the vessels are "very well hidden," explaining why it has taken so long for them to be identified. "It's so close to the blood vessel, you just miss it. If you don't know what you're after, you just miss it."
Could the presence of the vessels explain certain aspects of Alzheimer's?
For the UVa team, the discovery of the lymphatic vessels could lead to fresh explanations of how both the brain - and the diseases affecting it - function.
As an example, Prof. Kipnis points to the build-ups of protein in the brain that are characteristic of Alzheimer's, suggesting these clumps may be accumulating because they are not being efficiently removed by the lymphatic vessels.
The team is keen to investigate how aging might affect the role the vessels play, too, noticing visible differences in the vessels that appear to relate to age.
Kevin Lee, chair of UVa's Department of Neuroscience, commented of the team's work:
"The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation - and they've done many studies since then to bolster the finding - that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."
UVa also credit the work of Tajie Harris, assistant professor of neuroscience and a member of the Center for Brain Immunology and Glia, and research associate Igor Smirnov for making live imaging of the vessels possible.
The researchers describe their findings in the journal Nature.